Management of Methotrexate in Patients with Active Infection

Infection Risk and Management

The British Journal of Dermatology recommends that methotrexate should be temporarily discontinued during severe infection or when infection is not responding to standard treatment, and can be restarted when the infection has cleared 1, 2
Low-dose methotrexate is associated with an increased risk of infection, particularly pneumonia, skin/soft tissue infections, and urinary tract infections, with most infections occurring within the first 18 months of treatment 1, 2, 3
Methotrexate is considered a relative contraindication in patients with active infectious disease, particularly chronic infections that are likely to be worsened by immunosuppressive effects 4

The British Journal of Dermatology recommends immediately discontinuing methotrexate in patients with severe infection or infection not responding to standard treatment 1, 2
Methotrexate should be permanently discontinued in patients who develop opportunistic infections 2, 3
Patients on methotrexate should be monitored carefully for signs of sepsis and treated accordingly during infection 1

The Journal of the American Academy of Dermatology recommends obtaining complete blood count with differential to assess for neutropenia or other cytopenias when infection develops, and monitoring renal function closely as decreased renal function can lead to increased methotrexate levels and toxicity 3, 4
Methotrexate can be restarted when the infection has cleared 1, 2
The British Journal of Dermatology recommends resuming regular monitoring schedule after restarting therapy 4

The British Journal of Dermatology recommends avoiding co-trimoxazole, trimethoprim, and other antifolate drugs in patients taking methotrexate due to risk of bone marrow suppression 5, 6
Methotrexate should be used with extreme caution in patients with comorbidities that increase infection risk, such as diabetes, and in patients with HIV or hepatitis 1, 5, 7
Drug interactions with antibiotics can increase methotrexate toxicity through reduced protein binding or decreased renal elimination 4, 5